Protein folding and assembly are central biological processes that must occur correctly for the proper functioning of all living cells. Many devastating human diseases, including neurodegenerative Alzheimer and Prion diseases, are the consequence of disarrayed protein folding and assembly. A relatively large amount of celtuiar activity is dedicated to ensure the correct folding and assembly of proteins. In the event of misfolding, proteins are driven to aggregation and degradation pathways. Degradation of misfolded proteins is crucial because they may form toxic aggregates, which can interfere with normal cellular functions. Assembly factors that minimize aggregation (chaperones and foldases) or remove aggregates (proteases) are therefore complementary cellular activities that are regulated in response to the protein-folding status of the cell. Studying the assembly of membrane proteins has been a challenging task owing to their complex folding behavior. However, a recent explosion in the structural resolution of many membrane proteins, including those included in this study, has given a renewed impetus to the field of membrane protein biogenesis. The proposed research is directed at understanding the assembly of a unique outer membrane protein of Escherichia coil, ToiC, which folds into a novel three-dimensional structure. The TolC protein carries out several medically and physiologically important functions including antibiotic efflux and toxin secretion. This research will identify and characterize intragenic and extragenic factors that contribute to TolC's assembly into trimeric barrels composed of alpha-helices and beta-strands. These aspects will be studied through exploiting genetic, molecular, and biochemical methods. The available data show that TolC follows an assembly pathway distinct from alt other outer membrane proteins studied so far, thus providing an opportunity to uncover novet principles governing outer membrane protein targeting and assembly.